Developing a comprehensive pharmacological migraine management plan can be a daunting task. In this chapter, we will cover typical medications used and the development of pharmacological plans for use during the acute migraine attack and longer term migraine management, as well as briefly covering Emergency Department management and inpatient management of migraine.

Spreading depression (SD) is a slowly propagating wave of neuronal and glial depolarization lasting a few minutes, that can develop within the cerebral cortex or other brain areas after electrical, mechanical or chemical depolarizing stimulations. Cortical SD (CSD) is considered the neurophysiological correlate of migraine aura. It is characterized by massive increases in both extracellular K+ and glutamate, as well as rises in intracellular Na+ and Ca2+. These ionic shifts produce slow direct current (DC) potential shifts that can be recorded extracellularly. Moreover, CSD is associated with changes in cortical parenchymal blood flow.

CSD has been shown to be a common therapeutic target for currently prescribed migraine prophylactic drugs. Yet, no effects have been observed for the antiepileptic drugs carbamazepine and oxcarbazepine, consistent with their lack of efficacy on migraine. Some molecules of interest for migraine have been tested for their effect on CSD. Specifically, blocking CSD may play an enabling role for novel benzopyran derivative tonabersat in preventing migraine with aura. Additionally, calcitonin gene-related peptide (CGRP) antagonists have been recently reported to inhibit CSD, suggesting the contribution of CGRP receptor activation to the initiation and maintenance of CSD not only at the classic vascular sites, but also at a central neuronal level. Understanding what may be lying behind this contribution, would add further insights into the mechanisms of actions for “gepants”, which may be pivotal for the effectiveness of these drugs as anti-migraine agents.

CSD models are useful tools for testing current and novel prophylactic drugs, providing knowledge on mechanisms of action relevant for migraine.

Assessing the risk of stroke in persons with migraine is complicated by the intricate relationship between these two conditions. Both migraine and stroke are common and co-morbidity may, in some cases, be coincidental. Given the overlap of clinical symptoms in stroke and migraine, each condition may also mimic the other. Numerous studies have, however, shown that migraine is an independent risk factor for stroke both during, and remote from, the migraine attack. Women of childbearing age and those with aura are at greatest risk of migraine-related stroke. Additional risk of stroke in migraineurs occurs in those using oral contraceptive pills and who smoke cigarettes. Elevated blood pressure, an important stroke risk factor, is less common in migraineurs. Acquired antiphospholipid antibodies, not clearly a cause of migraine per se, may raise the risk of infarction in migraineurs. Hereditary conditions, including CADASIL (cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy), MELAS (mitochondrial myopathy, encephalopathy, lactacidosis and stroke) and hereditary haemorrhagic telangiectasia, appear to predispose to both migraine and stroke. Purported mechanisms for migraine-associated stroke include involvement of the vasculature (including vasospasm, arterial dissection and small vessel arteriopathy), hypercoagulability (elevated von Willebrand Factor, platelet activation) and elevated risk of cardioembolism (patent foramen ovale, atrial septal aneurysm). Triptans and ergotamines, used to treat acute migraine attacks, appear to be safe in low-risk populations. These medications should be avoided in persons with haemiplegic migraine, basilar migraine, vascular risk factor and prior cerebral or cardiac ischaemia.

Frequent, severe and long-lasting migraine attacks require prophylaxis. Established drugs used for the prevention of migraine such as β-adrenoceptor antagonists (β-blockers), calcium channel antagonists, antidepressants and others have an unknown mode of action in migraine. Their prophylactic effect in migraine was discovered by chance in clinical practice when these drugs were used for other purposes. Recently, research into the mechanisms of migraine and the progressive recognition that cortical hyperexcitability and an imbalance between neuronal inhibition [mediated by γ-aminobutyric acid (GABA)] and excitation (mediated by excitatory amino acids) may play an important role in migraine pathophysiology have lead to the identification of potential new agents for the prevention of migraine attacks. This paper reviews the recent literature on these new agents.

A search was conducted using MEDLINE from 1998 to November 2001 with the following search terms: migraine, preventive, prophylactic and treatment. Headache textbooks edited in 2000 and 2001 were also used.

After analysing the available controlled and uncontrolled clinical studies as well as abstracts, divalproex sodium (valproate semisodium) can be recommended for the prevention of migraine. Lamotrigine may be useful for preventing aura associated with migraine, and topiramate seems a promising option pending trials with more patients, which are currently underway. Riboflavin (which is possibly involved in improving neuronal energy production) appears to be a promising agent, although comparisons with established prophylactic medications are needed. Gabapentin, magnesium, lisinopril and botulinum toxin A have recently been suggested to be effective; however, at present, there are insufficient rigorous and reliable controlled data on these drugs for them to be indicated for such use. Emerging options such as tiagabine, levetiracetam, zonisamide and petasites may all be useful, but controlled data are required to confirm their efficacy. The anti-asthma medication montelukast was found to be effective in an open trial, but ineffective in a recently completed controlled trial.

There is an expectation that modern neuroscience will soon provide more efficacious and better tolerated prophylactic medications for migraine.

Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Monoclonal antibodies against CGRP (LY2951742, ALD-403, and LBR-101/TEV-48125) or its receptor (AMG334) were subsequently developed. As reviewed in this study, numerous phase 1 and 2 trials and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Being macromolecules, these mAbs are not suitable for oral administration; however, their intravenous or subcutaneous delivery can be performed at relatively low frequency—every month or even quarterly—which enhances patients’ compliance. Although not all migraineurs respond to this treatment, and longer administration periods will be needed to assess long-term effects, the results so far obtained are extraordinarily promising. The future introduction of mAbs on the market will probably represent a turning point for prevention similar to that represented by triptans for abortive treatment in migraine.

Migraine is a common disorder characterised by recurrent episodes of disability. Despite the high prevalence of migraine, data have been lacking on its impact in a working population. The advent of new therapies has stimulated interest in this area, and evidence is now available that documents the substantial impact of migraine on workplace productivity and the likelihood of untreated migraine leading to unemployment or underemployment for the patient.

This paper reviews current findings of both observational and interventional studies about the impact of migraine on productivity and employment. When considered in the light of migraine demographics, the high prevalence of migraine, and its low consultation and treatment rates, this evidence indicates that improved screening and treatment for this common condition could have a substantial impact on worker productivity and on patient well-being.

Individually, childhood epilepsy and migraine are two of the most common conditions seen in pediatric neurology. What complicates matters is that there can be marked similarities between migraine and epilepsy as well as a variety of underlying conditions that predispose children to both seizures and headache. Thus, separating epilepsy from migraine may not be easy, but can be done with a detailed history as well as timely use of ancillary testing. Once children have been diagnosed with epilepsy, migraine, or both, treatment options become essential in attempts to manage these common, yet often disabling, neurological conditions. Acute interventions tend to be condition specific while preventative options may overlap for migraine and epilepsy. In the following review, we will discuss the epidemiology of childhood epilepsy and headache, the association between them, as well as how to differentiate epilepsy from migraine. Treatment strategies will follow before concluding with a discussion on prognosis.